(a) Field of the Invention
The invention relates to the monitoring and/or prognostic of antibody-mediated autoimmune diseases, and treatments thereof.
(b) Description of Prior Art
Systemic lupus erythematosus (SLE) is a disease that predominantly affects women, and is characterized by high levels of circulating autoantibodies, which are thought to play an integral role in its pathogenesis. Most of the autoantibodies are specific for proteins that are normally sequestered inside the cell. Much recent interest has focused on the role that apoptosis plays in the movement of these autoantigens to blebs at the cell surface. We speculate that if this happened every time apoptosis occurred, inflammation would occur throughout the body in individuals with high levels of these circulating autoantibodies. This, however, does not occur in SLE, where the disease is more tissue specific with skin lesions and arthritis the most common features. Less common, but generally associated with morbidity, are the renal complications. We reasoned that there must be another level of control, which leads to the inflammation at the different sites. One protein of interest is clusterin, which is induced by the same stimuli that induce apoptosis, such as TNF, UVB irradiation, and serum deprivation.
Clusterin (also known as apoJ, and complement lysis inhibitor) is a 70-80 kD heterodimeric sulfated glycoprotein that is expressed by a large number of cells, including epithelial, polymorphonuclear and neuronal cells, as well as platelets. It has a protective role, and its expression at sites of tissue remodeling and apoptosis is thought to prevent antibody mediated lysis and inflammation. Clusterin not only binds and inhibits the terminal components of complement, but also binds immunoglobulin, apo-IA, and TGF receptors (both type I and II).
It would be highly desirable to be provided with means to monitor antibody-mediated autoimmune diseases.